张力素
伤口愈合
脐静脉
血管生成
下调和上调
PTEN公司
癌症研究
细胞生物学
生物医学工程
医学
化学
外科
生物
信号转导
PI3K/AKT/mTOR通路
生物化学
基因
体外
作者
Qian Wei,Jianlong Su,Sheng Meng,Yaxi Wang,Kui Ma,Bingmin Li,Ziqiang Chu,Qilin Huang,Wenzhi Hu,Zihao Wang,Lige Tian,Xi Liu,Tanshi Li,Xiaobing Fu,Cuiping Zhang
标识
DOI:10.1002/advs.202307761
摘要
Delayed wound healing is a major complication of diabetes, and is associated with impaired cellular functions. Current treatments are unsatisfactory. Based on the previous reports on microRNA expression in small extracellular vesicles (sEVs), miR-17-5p-engineered sEVs (sEVs17-OE) and encapsulated them in gelatin methacryloyl (GelMA) hydrogel for diabetic wounds treatment are fabricated. SEVs17-OE are successfully fabricated with a 16-fold increase in miR-17-5p expression. SEVs17-OE inhibited senescence and promoted the proliferation, migration, and tube formation of high glucose-induced human umbilical vein endothelial cells (HG-HUVECs). Additionally, sEVs17-OE also performs a promotive effect on high glucose-induced human dermal fibroblasts (HG-HDFs). Mechanism analysis showed the expressions of p21 and phosphatase and tensin homolog (PTEN), as the target genes of miR-17-5p, are downregulated significantly by sEVs17-OE. Accordingly, the downstream genes and pathways of p21 and PTEN, are activated. Next, sEVs17-OE are loaded in GelMA hydrogel to fabricate a novel bioactive wound dressing and to evaluate their effects on diabetic wound healing. Gel-sEVs17-OE effectively accelerated wound healing by promoting angiogenesis and collagen deposition. The cellular mechanism may be associated with local cell proliferation. Therefore, a novel bioactive wound dressing by loading sEVs17-OE in GelMA hydrogel, offering an option for chronic wound management is successfully fabricated.
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